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Objectives - high yield, affordable, water-friendly purification

DiViNe will make a real-life demonstration of the concept of affinity chromatography for vaccines purification, aiming at an even better performance than the Protein A-based processes with antibodies, combined with a self-sustainable approach for water resources.

High yield vaccine purification process

The downstream process for vaccine targets, ranging from simple proteins to complex virus like particles and glycoconjugates, comprises multiple steps: precipitation, folding, filtration, chromatography (anion and cation exchange) and crystallization. Affinity capture implementation has proven extremely successful in the purification of monoclonal antibodies in particular, with a potential gain in yield from 10% to 90% at the sole stage of affinity purification. Thus a 3 to 5-fold increase in recovery yield is expected, based on the results obtained in other affinity purification processes.

Drastic reduction in downstream processing costs

A major objective will be the simplification of the global chain of processing by reducing the steps to 2-3 consecutive operations centered on affinity capture as the major purification part. Such reduced number of steps will trigger a reduced operational cost. Moreover, Nanofitins® are easy to manufacture and the cost-of-goods will be compatible with the product cost-of-goods objectives, while Aquaporin Inside™ membranes will be available by the roll.

The low manufacturing costs of such elements make them compatible with a single-use approach, which might be even more cost-effective, as a simple column exchange between products will help save the time, fluids and verification steps induced by any Cleaning In Place (CIP) protocol. It might be of particular interest for infectious vaccines (virus-based).

Preserved product integrity

Harsh elution conditions may hamper the structure of the pharmaceutical product (enveloped vaccines and fragile antigens in particular), thereby generating new impurities and reducing the yield. Nanofitins® can be generated to bind the intended target on a specific epitope even under high concentration of impurities (concentrated cell media and debris) while eluting the target under conditions compatible with product integrity. The in vitro selection process allows such flexibility with a very moderate impact on timing. Aquaporin Inside™ membranes rely on active water transport, thereby creating almost no pressure nor shear stress. Combination of both technologies allows mild processes to be implemented.

Water-friendly purification process

Aquaporin technology lies in a water-purifying membrane coated with aquaporins, which can purify water by consuming only small amounts of energy. The innovation is based on the natural filtering ability of so-called aquaporins which, contrary to conventional methods, allows avoiding elaborate filtration systems typically based on energy- and cost-intensive hydrostatic pressure. As most fluids will be recycled for reuse, typically in early purification steps, the DiViNe purification process aim to set new standards for water consumption in downstream processing.

Transfer to other Biologics

When it comes to downstream processing of biologics, vaccines represent the most complex case (complex antigens, extreme safety concerns, high pressure on costs). Once validated on vaccines, the DiViNe platform will be implemented for recombinant proteins, monoclonal antibodies and fragments, and blood products. Major tunable parts are the cell harvest, the Nanofitins® developed specifically for each target in 3 months and the final formulation, although the equipment may be the same.

Through such demonstration on the most representative vaccines (glycoconjugates, protein antigens and enveloped viruses), the consortium will establish a sustainable platform to design custom, affordable, industry-compliant and environment-friendly purification processes of biologics. The target market will broadly expand beyond vaccines, up to complex recombinant products, gene therapy vectors, or blood products.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement Nº 635770